1. Field of the Invention
This invention relates to new Aspergillus niger mutants for identifying active FK-506/rapamycin type or cyclosporin A type immunosuppressants. Specifically disclosed are the new mutants, Aspergillus niger, (Merck Culture Collection No. MF 5659) ATCC No. 74085; ATCC No. 74086 (MF 5660); and ATCC No. 74087 (}iF 5661).
2. Brief Description of Disclosures in the Art
In 1983, the US FDA approved cyclosporin A, (see U.S. Pat. No. 4,117,118 to Sandoz) an effective anti-rejection drug that revolutionized the field of organ transplant surgery. The drug acts by inhibiting the body's immune system from mobilizing its vast arsenal of natural protecting agents to reject the transplant's foreign protein.
As effective as the drug is in fighting transplantation rejection, it suffers drawbacks in causing kidney failure, liver damage and ulcers which in many cases can be very severe.
EPO Publication No. 0184162 to Fujisawa, now issued as U.S. Pat. No. 4,894,366 hereby incorporated by reference, describes a new macrolide immunosuppressant FK-506 which is reputed to be 100 times more effective than cyclosporin. The macrolide is produced by fermentation of a particular strain of Streptomyces tsukubaensis. Also described is the closely related macrolide immunosuppressant FK-520, (FK-900520) produced by S. hygroscopicus subsp. yakushimaensis.
U.S. Pat. No. 3,929,992 to Ayerst discloses the macrolide compound rapamycin and its antibiotic and antifungal properties. Recent publications, (see J. of Immunology Vol. 144, p. 251-258 (No. 1&gt;, Jan. 1990 by F. J. Dumont et. al.,) disclose the use of the compound additionally as an immunosuppressant.
In the search for new immunosuppressant analogs, it would be helpful to have a single, convenient diagnostic assay, not involving laboratory animals, to selectively establish the presence of either FK-506/rapamycin type or cyclosporin A type immunosuppressant activity, in an unknown fermentation broth, natural product extract, e.g. human serum, plant extracts, or unknown composition, which displays immunosuppressant activity.